Chronic Pancreatitis

By assistant lecturer

MOHAMMAD EL-SAYED
• Chronic pancreatitis is defined as a
continuing chronic inflammatory process of
the pancreas, characterized by irreversible
morphological changes.
• This chronic inflammation can lead to
chronic abdominal pain and/or impairment of
endocrine and exocrine function of the
pancreas.
• By definition, chronic pancreatitis is a
completely different process from acute
pancreatitis. In acute pancreatitis, the patient
presents with acute and severe abdominal
pain, nausea, and vomiting.
• The pancreas is acutely inflamed
(neutrophils and edema), and the serum
levels of pancreatic enzymes (amylase and
lipase) are elevated.
• Full recovery is observed in most patients
with acute pancreatitis, whereas in chronic
pancreatitis, the primary process is a chronic
irreversible inflammation (monocyte and
lymphocyte) that leads to fibrosis with
calcification.
 Epidemiology:
1-Frequency
In the US: approximately 87,000 cases of
pancreatitis occur annually.
• Internationally: Comparing the hospital
admissions data from several cities around
the globe, the overall frequency is similar.
 II-Sex:
• Males are affected more commonly than
females (6.7 vs 3.2 per 100,000 population).
• Alcohol-induced illness is more prevalent in
males, idiopathic and hyperlipidemic-induced
pancreatitis is more prevalent in females,
and equal sex ratios are observed in chronic
pancreatitis associated with hereditary
pancreatitis.
 III-Age:
• The mean age at diagnosis is 46 years, plus
or minus 13 years.
• In idiopathic chronic pancreatitis, a bimodal
age distribution has been reported,
designated as early-onset form (median age
19.2 y) and late-onset form (median age 56.2
y).
 IV-Race:
• Hospitalization rates for blacks are 3 times
higher than for whites in the United States.
 Pathophysiology:
• Intraductal plugging and obstruction (eg,
alcohol abuse, stones, tumors).
• Direct toxins and toxic metabolites ( These
act on the pancreatic acinar cell to stimulate
the release of cytokines, which stimulate the
stellate cells to produce collagen and to
establish fibrosis) (eg. Alcohol, drugs).
• Oxidative stress (eg, alcohol, smoking).
• Necrosis-fibrosis (recurrent acute
pancreatitis that heals with fibrosis).
• Ischemia (from obstruction and fibrosis)
which is important in exacerbating disease
rather than in initiating disease.
• Autoimmune disorders: Chronic pancreatitis
has been found in association with other
autoimmune diseases, such as Sjögren
syndrome, primary biliary cirrhosis, and
renal tubular acidosis.
Aetiology:
I-Metabolic:
1-Excessive alcohol consumption is the most
common cause, accounting for about 60% of
all cases.
• In the affected gland, alcohol appears to
increase protein secretion from acinar cells
while decreasing fluid and bicarbonate
production from ductal epithelial cells.
• The resulting viscous fluid results in
proteinaceous debris becoming inspissated
within the lumen, causing ductular
obstruction.
• A competing theory suggests that the
persistent demands of metabolizing alcohol
causes oxidative stress within the pancreas
and may lead to cellular injury and organ
damage, especially in the setting of
malnutrition.
• Although 60-70% of chronic pancreatitis
cases are due to alcohol consumption, only
10-15 % of alcoholics develop chronic
pancreatitis.
• Other factors may be involved including high
fat and protein diet, deficiency in
antioxidants and trace elements, smoking
and genetic predisposition.
2-Hyperlipidemia (usually type I and type V)
also may cause chronic pancreatitis;
however, it usually presents with repeated
attacks of acute pancreatitis.
3-Hypercalcemia due to hyperparathyroidism
now is a rare cause of chronic pancreatitis,
probably because automation of serum
chemistries reveals hypercalcemia before it
results in pancreatitis.
4-Nutritional, or tropical, chronic pancreatitis is
rare in the United States, but it is an
important cause of disease in other parts of
the world.
II-Genetic:
1-Hereditaty pancreatitis Autosomal dominant
disorder accounting for about 1% of cases.
2-Cystic fibrosis is one of the most common
genetic abnormalities, is an autosomal
recessive disorder accounting for a small
percent of patients with chronic pancreatitis.
III-Idiopathic chronic
pancreatitis:
Accounts for approximately 30% of cases,
has been subdivided into early-onset and
late-onset forms. The cause is not yet known.
IV-Obstruction of the flow of
pancreatic juice can cause chronic
pancreatitis:
• Congenital abnormalities such as pancreas
divisum.
• Acquired obstructive forms result from blunt
abdominal trauma, stones or tumours.
V-Autoimmune pancreatitis:
• Is uncommon and accounts probably for less
than 1% of cases of chronic pancreatitis.
Clinical characteristics include diffuse
enlargement of the pancreas, diffuse and
irregular narrowing of the main pancreatic
duct, increased circulating levels of gamma
globulin (IgG4), the presence of
autoantibodies, and a possible association
with other autoimmune diseases.
 Clinical picture:
• Abdominal pain:
• The most common symptom.
• The patient experiences intermittent attacks
of severe pain, often in the mid or left upper
abdomen and occasionally radiating to the
back and lasting for several hours.
• A small percentage of patients (20%) have
painless chronic pancreatitis and present
with signs or symptoms of pancreatic
exocrine or endocrine insufficiency.
• Other symptoms associated with chronic
pancreatitis include diarrhea and weight
loss. This may be due either to fear of eating
(eg, postprandial exacerbation of pain) or
due to pancreatic exocrine insufficiency and
steatorrhea).
 Examination:
• During an attack, patients may assume a
characteristic position in an attempt to
relieve their abdominal pain (leaning
forward).
• Occasionally, a tender fullness or mass may
be palpated in the epigastrium, suggesting
the presence of a pseudocyst or an
inflammatory mass in the abdomen.
• Patients with advanced disease (ie, patients
with steatorrhea) exhibit decreased
subcutaneous fat, temporal wasting, sunken
supraclavicular fossa, and other physical
signs of malnutrition.
 Complications:
• Pseudocyst.
• Secondary infection.
• Mechanical obstruction of the duodenum and
common bile duct.
• Pancreatic ascites.
• Pleural effusion.
• Splenic vein thrombosis with portal
hypertension.
• Pseudoaneurysm of splenic artery.
• Diabetes mellitus is a late manifestation in
about one third of patients. The tendency to
develop ketoacidosis is low.
 Investigations:
1-Blood tests
• Serum amylase and lipase levels may be
slightly elevated in chronic pancreatitis; high
levels are found only during acute attacks of
pancreatitis.
• While low concentrations of serum trypsin
are relatively specific for advanced chronic
pancreatitis, they are not sensitive enough to
be helpful in most patients with mild-to-
moderate disease.
• Laboratory studies to identify causative
factors include serum calcium and
triglyceride levels.
 2-Fecal tests:
• Neither qualitative nor quantitative fecal fat
analysis can detect early disease because
maldigestion and malabsorption do not
occur until more than 90% of the pancreas
has been destroyed, steatorrhea is a
manifestation of advanced chronic
pancreatitis.
• Assays of fecal chymotrypsin and human
pancreatic elastase 1 have the same
limitations but are useful in confirming
advanced chronic pancreatitis with exocrine
insufficiency.
3-Pancreatic function tests:
A-Direct tests: These tests are the most
sensitive and can be used to detect chronic
pancreatitis at its earliest stage; however,
they are somewhat invasive, and expensive.
• Determination in duodenal aspirates:
Intubation of the duodenum usually is
performed. The output of pancreatic
bicarbonate, protease, amylase, and lipase
then is measured in the duodenal aspirates.
• Determination in pancreatic juice: This test
generally is performed in conjunction with
(ERCP). The pancreatic duct is freely
cannulated, and the pancreatic juice then is
aspirated out of the duct as it is produced.
The output of pancreatic bicarbonate,
protease, amylase, and lipase are measured.
 B-Indirect tests:
• Noninvasive tests of pancreatic function
have been developed for detecting chronic
pancreatitis.
• In principle, these tests work via oral
administration of a complex substance
(bentiromide) that is hydrolyzed by a specific
pancreatic enzyme to release a marker
substance (PABA).
• The intestine absorbs the marker, which then
is measured in the serum or urine. These
tests are capable of detecting moderate-to-
severe chronic pancreatitis.
• The presence of renal, intestinal, and liver
disease may interfere with the accuracy of
these tests.
4-Imaging studies:
A-Abdominal x-ray:
Pancreatic calcifications, often considered
pathognomonic of chronic pancreatitis, are
observed in approximately 30% of cases.
B-Abdominal US:
Can reveal pancreatic duct dilatation,
calcifications, pseudocysts, pancreatic
ductal stones.
 C-EUS:
To diagnose chronic pancreatitis requires the
presence of at least 3 criteria of the
followings:
• Ductal findings: dilated main duct, duct
irregularities, hyperechoic duct margins,
stones and calcifications.
• Parenchymal findings:
hyperechoic foci, hyperechoic strands, gland
lobularity and cystic cavities.
D-Computed tomography scan:
Pseudocysts, calcifications and pncreatic
duct dilatation can be observed in chronic
pancreatitis.
 E-MRCP:
• Noninvasive
• It can assess both pancreatic parenchyma
and ducts at the same time.
• It can detect pancreatic duct dilatation,
ductal narrowing and filling defects.
 F-ERCP:
• Provides the most accurate visualization of
the pancreatic ductal system and has been
regarded as the criterion standard for
diagnosing chronic pancreatitis.
• Findings include characteristic “chain of
lakes” beading of the main pancreatic duct,
and intraductal filling defects.
Treatment:
1-Behavior modification:
Cessation of alcohol consumption and
tobacco smoking are important. In early-
stage alcohol-induced chronic
pancreatitis, lasting pain relief can occur
after abstinence from alcohol, but, in
advanced stages, abstinence does not
always lead to symptomatic improvement.
• Patients continuing to abuse alcohol
develop either marked physical
impairment or have a death rate 3 times
higher than those abstaining.
2-Medical tratment:
A-Analgesics: to relieve tha abdominal pain.
B-Hormones: Reduction of pancreatic exocrine
secretion. Subcutaneous injection of
octreotide (Sandostatin) at 200 mcg tid
provided relief of pain in 66% of patients.
 C-Antidepressants: (Amitriptyline
hydrochloride)
• In addition to alleviating coexistent
depression, tricyclic antidepressants may
ameliorate pain and potentiate the effects of
opiates.
 D-Pancreas enzyme supplements:
• Used as a dietary supplement to aid
digestion in patients with pancreatic enzyme
deficiency. Several preparations are
available. Eg. Pancrelipase: assists in
digestion of protein, starch, and fat.
3-Endoscopic treatment:
I-Papillary stenosis: In appropriately selected
patients, a pancreatic duct sphincterotomy
will facilitate drainage, reduce ductal
pressures, and may help alleviate pain.
II-Pancreatic duct strictures: performing a
pancreatic sphincterotomy, dilating the
stricture, and placing a stent. While technical
success is achieved in more than 90% of
patients, nearly 20% will have a complication.
 III-Pancreatic duct stones:
• Requires a pancreatic duct sphincterotomy
and stricture dilation to enable their
extraction.
• In addition to various endoscopic
techniques, extracorporeal shockwave
lithotripsy often is necessary to break up
impacted or large stones into smaller pieces
suitable for removal.
 IV-Pancreatic pseudocysts:
• Noncommunicating pseudocysts that bulge
into the foregut are treatable by endoscopic
transduodenal or transgastric
pseudocystostomy.
• The success rate is 85%, with a 17%
complication rate, and the transduodenal
approach has fewer complications and
recurrences than the transgastric approach.
4-Surgical treatment:
I-Pancreatic duct drainage: In patients with a
dilated pancreatic duct,
pancreaticojejunostomy is indicated. The
operative mortality rate is about 3%, and pain
relief is obtained in approximately 75% of
patients.
II-Pancreatic resection: If the disease is limited
to the head of the pancreas, a Whipple
operation (pancreaticoduodenectomy) can
produce good results.
• In patients with intractable pain and diffuse
disease with nondilated ducts, a subtotal or
total pancreatectomy can be offered.
 III-Total pancreatectomy and islet
autotransplantation:
In selected patients, the long-term morbidity
caused by diabetes following total
pancreatectomy can be avoided.
• This involves harvesting the islets from the
resected pancreas and injecting them into
the portal system, which then lodges them in
the liver.
IV- Drainage of pseudocyst:
The indications include rapid enlargement,
compression of surrounding structures
(duodenal, biliary obstruction or vascular
occlusion), pain, or signs of infection and
abscess formation, suspected malignancy,
hemorrhage and intraperitoneal rupture.
 Prognosis:
• The prognostic factors associated with
chronic pancreatitis are age at diagnosis,
smoking, continued use of alcohol, and the
presence of liver cirrhosis.
• The overall survival rate is 70% at 10 years
and 45% at 20 years.
• The risk of developing pancreatic cancer is
approximately 4% at 20 years.